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1.
Article in Chinese | WPRIM | ID: wpr-928745

ABSTRACT

OBJECTIVE@#To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis.@*METHODS@#Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database.@*RESULTS@#There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database.@*CONCLUSION@#These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.


Subject(s)
Computational Biology , Gene Expression , Gene Expression Profiling , Humans , Microarray Analysis , Myelodysplastic Syndromes/genetics , Protein Interaction Maps
2.
Article in English | WPRIM | ID: wpr-928657

ABSTRACT

To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.


Subject(s)
Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Protein Interaction Maps
3.
Int. braz. j. urol ; 47(4): 843-855, Jul.-Aug. 2021. tab, graf
Article in English | LILACS | ID: biblio-1286781

ABSTRACT

ABSTRACT Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. Materials and Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.


Subject(s)
Humans , Cystitis, Interstitial/genetics , Software , Gene Expression Profiling , Protein Interaction Maps/genetics , Gene Ontology
4.
Article in English | WPRIM | ID: wpr-922585

ABSTRACT

OBJECTIVES@#The biomarkers targeting colorectal cancer (CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC.@*METHODS@#GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa (CRM) tissues from the NCBI-GEO database, and the differentially expressed genes (DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC.@*RESULTS@#For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets (|log@*CONCLUSIONS@#The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Computational Biology , Formins , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Glycoproteins , Humans , Intercellular Signaling Peptides and Proteins , Oncogenes , Prognosis , Protein Interaction Maps
5.
Article in English | WPRIM | ID: wpr-921385

ABSTRACT

OBJECTIVES@#To identify the differentially expressed genes (DEGs) during the pathogenesis of periodontitis by bioinformatics analysis.@*METHODS@#GEO2R was used to screen DEGs in GSE10334 and GSE16134. Then, the overlapped DEGs were used for further analysis. g:Profiler was used to perform Gene Ontology analysis and pathway analysis for upregulated and downregulated DEGs. The STRING database was used to construct the protein-protein interaction (PPI) network, which was further visua-lized and analyzed by Cytoscape software. Hub genes and key modules were identified by cytoHubba and MCODE plug-ins, respectively. Finally, transcription factors were predicted via iRegulon plug-in.@*RESULTS@#A total of 196 DEGs were identified, including 139 upregulated and 57 downregulated DEGs. Functional enrichment analysis showed that the upregulated DEGs were mainly enriched in immune-related pathways including immune system, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and chemokine receptors bind chemokines. On the contrary, the downregulated DEGs were mainly related to the formation of the cornified envelope and keratinization. The identified hub genes in the PPI network were CXCL8, CXCL1, CXCR4, SEL, CD19, and IKZF1. The top three modules were involved in chemokine response, B cell receptor signaling pathway, and interleukin response, respectively. iRegulon analysis revealed that IRF4 scored the highest.@*CONCLUSIONS@#The pathogenesis of periodontitis was closely associated with the expression levels of the identified hub genes including CXCL8, CXCL1, CXCR4, SELL, CD19, and IKZF1. IRF4, the predicted transcription factor, might serve as a dominant upstream regulator.


Subject(s)
Computational Biology , Gene Expression Profiling , Humans , Microarray Analysis , Periodontitis , Protein Interaction Maps
6.
Braz. j. med. biol. res ; 54(11): e11363, 2021. graf
Article in English | LILACS | ID: biblio-1339445

ABSTRACT

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms/genetics , Papillomavirus Infections , Gene Expression Regulation, Neoplastic , Cell Cycle/genetics , Kinesins/genetics , Oncogene Proteins , Disease-Free Survival , Computational Biology , Protein Interaction Maps
7.
Braz. arch. biol. technol ; 64: e21200118, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339316

ABSTRACT

Abstract This paper focuses on developing a reduced distance matrix to improve the computational performance during the protein interactions clustering. This proposed matrix considers as centroids two alpha carbon atoms from a protein structure and stores the distances between these centroids and the other atoms from this same structure. Each row in this matrix represents a database record and each column is a distance value. Through this build matrix, clusters were performed using K-Means Clustering. The precision and performance of this presented technique were compared with aCSM, RID and another distance matrix methodology that considers the distances between all atoms from each protein structure. The results were satisfactory. The reduced distance matrix obtained a high precision and the best computational performance.


Subject(s)
Protein Interaction Maps , Carbon , Cluster Analysis , Computing Methodologies
8.
Article in Chinese | WPRIM | ID: wpr-879142

ABSTRACT

To probe the potential hepatotoxic components of Epimedii Folium and investigate its mechanism based on network toxicology and cell experimental validation. According to the previous results of component measurement and cytotoxicity evaluation, 11 active compounds related to hepatotoxicity in Epimedii Folium were chosen as research object in this study. Through SwissTargetPrediction database and GeneCards database, the potentially hepatotoxic targets of Epimedii Folium were obtained. Subsequently, the protein-target interaction network and active compounds-hepatotoxic targets network were established to analyze the core targets and screen the key hepatotoxic compounds in Epimedii Folium. Meanwhile, the signaling pathways and molecular mechanisms were inferred with GO functional enrichment analysis and KEGG pathway enrichment analysis on the core targets. At last, the effect of icaritin as the chief hepatotoxic compound on the indexes related to hepatotoxicity in HL-7702 cells and HepG2 cells was investigated to validate the hepatotoxicity mechanism of Epimedii Folium. Through the network toxicology analysis, 190 action targets and 991 hepatotoxic targets were collected, then 64 potentially hepatotoxic targets of Epimedii Folium including AKT1, EGFR, MAPK3, TNF and so on were obtained, and icaritin was screened as the key hepatotoxic compound. GO functional enrichment analysis indicated 160 biological process terms such as protein phosphorylation and negative regulation of apoptotic process, 41 molecular function terms such as protein binding and ATP binding, and 32 cellular component terms such as cytosol and cell surface. KEGG pathway enrichment analysis inferred 75 signaling pathways involving PI3 K-Akt and HIF-1. After comprehensive analysis, it was inferred that the hepatotoxicity mechanism of Epimedii Folium was related with regulating oxidative stress and apoptosis. The results of cell biology experiments showed that icaritin could significantly increase the level of aspartate aminotransferase and lactate dehydrogenase, reduce the level of glutathione, improve the quality of reactive oxygen species and reduce mitochondrial membrane potential, indicating that it could cause hepatotoxicity by destroying cell membrane structure, inhibiting antioxidant enzyme activity, activating oxidative stress and inducing apoptosis. These results proved the reliability of results of network pharmacology. This study preliminarily clarified the material base and the mechanism of potential hepatotoxicity of Epimedii Folium, which provided important information for further research and safe application.


Subject(s)
Drugs, Chinese Herbal/toxicity , Plant Leaves , Protein Interaction Maps , Reproducibility of Results
9.
Article in Chinese | WPRIM | ID: wpr-888154

ABSTRACT

Magnoliae Officinalis Cortex(Houpo) can treat peptic ulcer disease(PUD), the mechanism of which remains unclear. In this study, network pharmacology and molecular docking were employed to predict the mechanism of Houpo in the treatment of PUD. Through literature review and TCMSP screening, 15 main active ingredients were obtained. The SwissTargetPrediction database was used to predict the potential targets of the ingredients, and Therapeutic Target Database(TTD), DrugBank, and Human Phenotype Ontology(HPO) to screen the disease-related targets. A total of 49 potential targets were obtained by the intersection of active ingre-dients-related targets and disease-related targets. Cytoscape 3.6.1 was employed to construct the protein-protein interaction network for the targets with high confidence(score>0.700) screened out by STRING. The DAVID database was used for GO and KEGG pathway enrichment of potential targets. GO enrichment analysis showed that the treatment mechanism was mostly related to nuclear receptor activity, ligand-activated transcription factor activity, and G protein-coupled acetylcholine receptor activity. KEGG enrichment analysis found that Houpo could regulate material metabolism, endocrine system, p53 signaling pathway, and PPAR signaling pathway. Molecu-lar docking verified that all 15 ingredients had good binding activities with key targets(CHRM1, CHRM2, FABP1, mTOR, and STAT3). The results mean that Houpo can treat PUD by participating in cell metabolism, inhibiting inflammatory cytokines, and regulating cell proliferation and apoptosis.


Subject(s)
Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Peptic Ulcer , Protein Interaction Maps , Receptor, Muscarinic M1 , Signal Transduction
10.
Article in Chinese | WPRIM | ID: wpr-888123

ABSTRACT

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Protein Interaction Maps , Qi , Vascular Endothelial Growth Factor A
11.
Article in Chinese | WPRIM | ID: wpr-887869

ABSTRACT

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With


Subject(s)
Biomarkers, Tumor/genetics , Carrier Proteins , Computational Biology , Cytochrome P-450 CYP2E1 , Cytochrome P-450 CYP3A , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Glycoproteins , Humans , Liver Neoplasms/genetics , Prognosis , Protein Interaction Maps
12.
Braz. j. med. biol. res ; 53(9): 0-0, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132553

ABSTRACT

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.


Subject(s)
Myocardial Reperfusion Injury , MicroRNAs , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Protein Interaction Maps , Gene Ontology
13.
Article in English | WPRIM | ID: wpr-880485

ABSTRACT

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.


Subject(s)
Acetylation , Lysine/metabolism , Oryza/metabolism , Plant Proteins/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Proteome/metabolism , Ubiquitin/metabolism , Ubiquitination
14.
Journal of Integrative Medicine ; (12): 229-241, 2020.
Article in English | WPRIM | ID: wpr-829101

ABSTRACT

OBJECTIVE@#Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.@*METHODS@#To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.@*RESULTS@#For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.@*CONCLUSION@#RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.


Subject(s)
Antiviral Agents , Chemistry , Therapeutic Uses , Betacoronavirus , Chemistry , Coronavirus Infections , Drug Therapy , Virology , Cysteine Endopeptidases , Chemistry , Drugs, Chinese Herbal , Chemistry , Therapeutic Uses , Humans , Mass Spectrometry , Medicine, Chinese Traditional , Molecular Docking Simulation , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Interaction Maps , Viral Nonstructural Proteins , Chemistry
15.
Article in Chinese | WPRIM | ID: wpr-828038

ABSTRACT

To explore the main target and signal pathway of Simiao Yongan Decoction in the treatment of psoriatic arthritis(PsA) by network pharmacology, so as to reveal the intervention mechanism of Simiao Yongan Decoction in the treatment of psoriatic arthritis. The platform of pharmacology technology of traditional Chinese medicine system(TCMSP) was used to predict and screen the active ingredients of Simiao Yongan Decoction, and GeneCards database was searched to obtain the disease target related to the psoriatic arthritis. Protein interaction network model was constructed with STRING platform; drug-component-target-disease network map was constructed with Cytoscape Software; Wayne Diagram of common target of Simiao Yongan Decoction and psoriasis arthritis was drawn with the help of ClusterProfiler R Software. At the same time, the genetic ontology(GO) enrichment analysis and the Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis were conducted. Through database analysis, 1 128 targets related to 70 main active components of Simiao Yongan Decoction and psoriatic arthritis were selected. On this basis, the interaction network between Simiao Yongan Decoction and psoriatic arthritis was constructed, and 38 common targets were screened out. By GO and KEGG enrichment analysis, 135 signal pathways related to the main components of Simiao Yongan Decoction were selected. It was found that Simiao Yong-an Decoction may play a role in the treatment of psoriatic arthritis through antiviral effect, anti-inflammatory repair, protection of vascular endothelial cells, regulation of immunity and other multiple targets. The mechanism of Simiao Yongan Decoction in the treatment of psoriatic arthritis from multi-component, multi-target and multi-pathway was revealed, which provided a research direction for screening its subsequent clinical effect evaluation indexes.


Subject(s)
Arthritis, Psoriatic , Drugs, Chinese Herbal , Endothelial Cells , Humans , Medicine, Chinese Traditional , Protein Interaction Maps
16.
Biol. Res ; 53: 24, 2020. tab, graf
Article in English | LILACS | ID: biblio-1124209

ABSTRACT

BACKGROUND: BMPR-1B is part of the transforming growth factor ß super family and plays a pivotal role in ewe litter size. Functional loss of exon-8 mutations in the BMPR-1B gene (namely the FecB gene) can increase both the ewe ovulation rate and litter size. RESULTS: This study constructed a eukaryotic expression system, prepared a monoclonal antibody, and characterized BMPR-1B/FecB protein-protein interactions (PPIs). Using Co-immunoprecipitation coupled to mass spectrometry (Co-IP/MS), 23 proteins were identified that specifically interact with FecB in ovary extracts of ewes. Bioinformatics analysis of selected PPIs demonstrated that FecB associated with several other BMPs, primarily via signal transduction in the ovary. FecB and its associated interaction proteins enriched the reproduction process via BMP2 and BMP4 pathways. Signal transduction was identified via Smads proteins and TGF-beta signaling pathway by analyzing the biological processes and pathways. Moreover, other target proteins (GDF5, GDF9, RhoD, and HSP 10) that interact with FecB and that are related to ovulation and litter size in ewes were identified. CONCLUSIONS: In summary, this research identified a novel pathway and insight to explore the PPi network of BMPR-1B.


Subject(s)
Animals , Female , Ovary/metabolism , Bone Morphogenetic Protein Receptors, Type I/genetics , Eukaryota/genetics , Protein Interaction Maps/genetics , Mass Spectrometry , Polymorphism, Restriction Fragment Length , Sheep , Signal Transduction , Polymerase Chain Reaction , Computational Biology , Bone Morphogenetic Protein Receptors, Type I/metabolism , Eukaryota/metabolism , Genotype , Mutation
17.
Article in Chinese | WPRIM | ID: wpr-773149

ABSTRACT

Xixian Tongshuan Capsules with functions of promoting blood circulation and removing blood stasis,dispelling wind and resolving phlegm,relaxing muscles and activating collaterals,restoring consciousness and inducing resuscitation,has significant effects on main and concurrently symptoms of apoplexy. In this research,908 chemical compounds of Xixian Tongshuan Capsules were collected,and 337 potential targets were discovered by pharmacophore based reverse target identification. Protein interaction network( PIN)was then constructed and Identifying Protein Complex Algorithm( IPCA) was used to obtain the modules of the capsule and analyze the potential action mechanism. According to the research,Xixian Tongshuan Capsules could play a therapeutic role for hyperlipidemia and hypertension by regulating lipid metabolic process and blood pressure,the most direct risk factors of apoplexy. It could be used to treat the cerebral thrombosis and irreversible death of nerve tissue caused by insufficient supply of cerebral tissue blood and oxygen,in a way of regulating blood circulation system and nervous system. Xixian Tongshuan Capsules could also treat stroke-induced inflammation and inflammatory immune response through its regulatory effect on inflammatory immune response. Based on the network analysis,the antiinflammatory activity of Xixian Tongshuan Capsules extracts was investigated by measuring the NO release with Griess reagent method through LPS-induced in vitro inflammation model of RAW264. 7 cells. The results showed that Xixian Tongshuan Capsules extracts inhibited the secretion of NO by LPS-induced RAW264. 7 cells,indicating favorable anti-inflammatory activity. This research illuminates the mechanism of Xixian Tongshuan Capsules based on the PIN analysis at molecular network level,providing a scientific basis for its clinical application.


Subject(s)
Animals , Capsules , Drugs, Chinese Herbal , Pharmacology , Humans , Inflammation , Drug Therapy , Mice , Nitric Oxide , Metabolism , Protein Interaction Maps , Stroke , Drug Therapy
18.
Article in English | WPRIM | ID: wpr-761799

ABSTRACT

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.


Subject(s)
Animals , Biomarkers , Calcium , Calcium Signaling , Citric Acid , Citric Acid Cycle , Cytokines , Dermatitis, Atopic , Gene Ontology , Genome , Metabolism , Mice , Microarray Analysis , Mitochondria , Muscle Cells , Muscle Contraction , Muscle, Skeletal , Myoblasts , Myocardium , Oxidation-Reduction , Protein Interaction Maps , Pyroglyphidae , Receptors, Antigen, T-Cell , Skin
19.
Mem. Inst. Oswaldo Cruz ; 114: e180506, 2019. tab, graf
Article in English | LILACS | ID: biblio-990188

ABSTRACT

BACKGROUND Nicotinamide adenine dinucleotide (NAD) plays a central role in energy metabolism and integrates cellular metabolism with signalling and gene expression. NAD biosynthesis depends on the enzyme nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT; EC: 2.7.7.1/18), in which converge the de novo and salvage pathways. OBJECTIVE The purpose of this study was to analyse the protein-protein interactions (PPI) of NMNAT of Leishmania braziliensis (LbNMNAT) in promastigotes. METHODS Transgenic lines of L. braziliensis promastigotes were established by transfection with the pSP72αneoαLbNMNAT-GFP vector. Soluble protein extracts were prepared, co-immunoprecipitation assays were performed, and the co-immunoprecipitates were analysed by mass spectrometry. Furthermore, bioinformatics tools such as network analysis were applied to generate a PPI network. FINDINGS Proteins involved in protein folding, redox homeostasis, and translation were found to interact with the LbNMNAT protein. The PPI network indicated enzymes of the nicotinate and nicotinamide metabolic routes, as well as RNA-binding proteins, the latter being the point of convergence between our experimental and computational results. MAIN CONCLUSION We constructed a model of PPI of LbNMNAT and showed its association with proteins involved in various functions such as protein folding, redox homeostasis, translation, and NAD synthesis.


Subject(s)
Leishmania braziliensis , Protein Interaction Maps , NAD/analysis , Nicotinamide-Nucleotide Adenylyltransferase
20.
Article in Chinese | WPRIM | ID: wpr-687780

ABSTRACT

<p><b>OBJECTIVE</b>To identify hub genes and key pathways associated with anaplastic thyroid carcinoma (ATC), and to explore possible intervention strategy.</p><p><b>METHODS</b>The differentially expressed genes (DEGs) in ATC were identified by Gene Expression Omnibus (GEO) combined with using R language; the pathway enrichment of DEGs were performed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The protein-protein interaction (PPI) network of DEGs was constructed by STRING database and visualized by Cytoscape. Furthermore, the hub genes and key nodes were calculated by MCODE. Finally, the drug repurposing was performed by L1000CDS.</p><p><b>RESULTS</b>A total of 2087 DEGs were identified. The DEGs were clustered based on functions and pathways with significant enrichment analysis, among which PI3K-Akt signaling pathway, p53 signaling pathway, inflammatory response, extracellular matrix organization were significantly upregulated. The PPI network was constructed and the most significant three modules and nine genes were filtered. Twenty-two potential compounds were repurposed for ATC treatment.</p><p><b>CONCLUSIONS</b>Using integrated bioinformatics analysis, we have identified hub genes and key pathways in ATC, and provide novel strategy for the treatment of ATC.</p>


Subject(s)
Computational Biology , Drug Repositioning , Gene Expression Profiling , Humans , Phosphatidylinositol 3-Kinases , Protein Interaction Maps , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms
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